Genetic studies on ethanol toxicity can be divided into two parts: (i) to what extent do inborn factors predispose individuals to abusing alcohol? and (ii) to what extent do inborn factors predispose individuals who abuse alcohol to the development of specific complications? Although recent studies suggest that there are at least some populations in which there are important genetic predispositions to the development of alcoholism, the first question remains controversial. It is clear, however, that some patients are biologically predisposed to developing one or another complication if they abuse ethanol. Transketolase abnormality has been suggested to be one of the concomitants of thiamine deficiency disease. A well known example is Wernicke-Korsakoff syndrome. Recently, we have found that this enzyme abnormality is present at a higher frequency among alcoholic men than in their non-alcoholic counterpart and in their male progeny long before they abused alcohol. The inheritance pattern of this enzyme abnormality seems to be autosomal recessive in nature. Additionally, it appears that transketolase abnormality may also be responsible for many of the concomitants of fetal alcohol syndrome (FAS), namely, intrauterine growth retardation (IUGR), microcephaly and abnormal brain pathology. Preliminary data suggest that thiamine deficiency, a frequent complication in chronic alcoholism may contribute to IUGR and microcephaly in the rat and teratogenic effects of alcohol is dramatically increased when pregnant animals are rendered thiamine deficient. Since all chronic alcoholic pregnant women do not give birth to FAS children it is suggested that a genetic predisposition to thiamine deficiency (i.e. transketolase abnormality) may be responsible for this variability among individuals. Additionally, while investigating the effects of ethanol on opiate peptides we recently discovered that there are two pools of Beta-endorphin like immunoreactivity in blood of mice, rats, rabbits and humans. This is the first time an erythrocyte pool has been recognized.